TRAF3-interacting JNK-activating modulator

Definition:

Adapter protein that plays essential roles in both innate and adaptive immunity. Plays a crucial role in the regulation of thymocyte development. Mechanistically, mediates TCR-stimulated activation through recruiting MAP2K1/MEK1 to the Golgi and, thereby, facilitating the interaction of MAP2K1/MEK1 with its activator BRAF. Also plays an essential role in regulatory T-cell stability and function by recruiting the serine-threonine phosphatase catalytic subunit (PPP2CA) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component RPTOR and restricting glycolytic metabolism. Positively regulates TLR4 signaling activity in macrophage-mediated inflammation by acting as a molecular clamp to facilitate LPS-induced translocation of TLR4 to lipid rafts. In response to viral infection, facilitates the recruitment of TRAF3 to MAVS within mitochondria leading to IRF3 activation and interferon production. However, participates in the maintenance of immune homeostasis and the prevention of overzealous innate immunity by promoting 'Lys-48'-dependent ubiquitination of TBK1.

References:

[1]. Qiang Zou, et al. T cell development involves TRAF3IP3-mediated ERK signaling in the Golgi. J Exp Med. 2015 Jul 27;212(8):1323-36. [Content Brief]

[2]. Wenting Zhu, et al. TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiviral innate immunity. EMBO J. 2019 Sep 16;38(18):e102075. [Content Brief]

[3]. Xiaoyan Yu, et al. Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome. J Exp Med. 2018 Sep 3;215(9):2463-2476. [Content Brief]

[4]. Meng Deng, et al. TRAF3IP3 negatively regulates cytosolic RNA induced anti-viral signaling by promoting TBK1 K48 ubiquitination. Nat Commun. 2020 May 4;11(1):2193. [Content Brief]

[5]. Yehua Li, et al. TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts. J Biol Chem. 2019 Feb 22;294(8):2744-2756. [Content Brief]

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